title: RANKL expression is related to treatment outcome of patients with localized, high-grade osteosarcoma.
abstract: BACKGROUND
  The receptor activator of nuclear factor κB ligand (RANKL/TNFSF11) is expressed in metastatic bone cancer cells and has been suggested to play a key role in cell migration and metastatic behavior. We determined whether RANKL expression is correlated to clinical behavior of localized, high-grade osteosarcoma.
  
  
  METHODS
  This retrospective, immunohistochemical study was performed using materials obtained from 40 patients treated at Korea Cancer Center Hospital between 1995 and 2007. Prechemotherapy biopsy samples were stained for RANKL and correlations between RANKL expression and clinical characteristics and outcomes were evaluated. Staining was interpreted in a semiquantitative manner using an intensity based scoring system.
  
  
  RESULTS
  Thirty cases (75.0%) stained positively for RANKL; 15 (50.0%) had a high RANKL score (≥ 4) and the other 15 a low RANKL score (≤3). RANKL expression and RANKL scores were not related to age, sex, tumor location, tumor volume, or pathologic subtype. However, RANKL expression was related to a poor response to preoperative chemotherapy (P = 0.03) and a high RANKL score was associated with inferior survival. The 5-year event-free survival of patients with RANKL score ≥4 was 17.8 ± 10.5%, which was far worse than those with RANKL scores 1-3 or 0 (50.0 ± 15.8%, 56.0 ± 13.7%, respectively, P = 0.02).
  
  
  CONCLUSIONS
  The RANKL-RANK-OPG axis might be a promising target for the treatment of osteosarcoma, but further studies are needed to verify our data in a larger cohort.
authors.affiliation: Department of Pediatrics, Korea Cancer Center Hospital, Seoul, Republic of Korea.
authors.forename: Jun Ah
authors.initials: JA
authors.lastname: Lee
authors.forename: Jun Soo
authors.initials: JS
authors.lastname: Jung
authors.forename: Dong Ho
authors.initials: DH
authors.lastname: Kim
authors.forename: Jung Sub
authors.initials: JS
authors.lastname: Lim
authors.forename: Min Suk
authors.initials: MS
authors.lastname: Kim
authors.forename: Chang-Bae
authors.initials: CB
authors.lastname: Kong
authors.forename: Won Seok
authors.initials: WS
authors.lastname: Song
authors.forename: Wan Hyeong
authors.initials: WH
authors.lastname: Cho
authors.forename: Dae-Geun
authors.initials: DG
authors.lastname: Jeon
authors.forename: Soo-Yong
authors.initials: SY
authors.lastname: Lee
authors.forename: Jae-Soo
authors.initials: JS
authors.lastname: Koh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D053245:RANK Ligand / Q000378:metabolism*; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D053245:RANK Ligand; C505688:TNFSF11 protein, human